Targeting NAMPT using Novel Inhibitor RPT-E-037 in Pancreatic Neuroendocrine Tumor
Presenter: Md Hafiz Uddin, PhD Session: Novel Antitumor Agents 1 Time: 4/19/2026 2:00:00 PM → 4/19/2026 5:00:00 PM
Authors
Md Hafiz Uddin 1 , Husain Yar Khan 2 , Amro Aboukameel 3 , Sahar F. Bannoura 3 , Irfana Muqbil 4 , Hugo Jimenez 1 , Filza Khan 1 , Rafic Beydoun 3 , Gregory Dyson 3 , Yang Shi 3 , Mohammed N. Al Hallack 3 , Nitin Vaishampayan 3 , Ibrahim Azar 3 , Steve Kim 3 , Eliza W. Bael 3 , Miguel Tobon 3 , Khalil Choucair 3 , Walid Sukkari 1 , Hafsa Imtiaz 1 , Herbert Chen 3 , Muhammad W. Saif 3 , Anthony Frank Shields 5 , Ramzi M. Mohammad 3 , Philip Philip 6 , Bassel F. El Rayes 7 , Min Wu 8 , Michael Schelle 8 , Boris Pasche 3 , Asfar S. Azmi 3 1 Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, 2 Barbara Ann Karmanos Cancer Institute, Detroit, MI, 3 Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, 4 Lawrence Technological University, Southfield, MI, 5 Associate Director for Clinical Research, Barbara Ann Karmanos Cancer Institute, Detroit, MI, 6 Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI, 7 University of Alabama at Birmingham, Birmingham, AL, 8 Remedy Plan Therapeutics, Gaithersburg, MD
Abstract
Background and Objective: Advanced pancreatic neuroendocrine tumors (pNETs) respond poorly to current FDA-approved therapies, emphasizing the urgent need to find new and effective treatment targets. Nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in the NAD biosynthesis pathway, has emerged as a crucial therapeutic target in pNETs. Despite its importance, specific inhibitors directly targeting NAMPT for pNET treatment are currently lacking. This study aimed to evaluate the efficacy of RPT-E-037, a novel NAMPT inhibitor, in preclinical models of pNETs. Methods: Growth inhibition was determined by MTT, colony formation and apoptosis assays. We also measured growth arrest using cell cycle analysis. Expression of gene or protein was determined using quantitative PCR, and western blotting techniques. The impact of NAMPT inhibitor RPT-E-037 was evaluated in pNET in vitro cultures and in in vivo . Results: RPT-E-037 demonstrated its growth inhibitory effect in BON-1 and QGP-1 pNET cell lines at pharmacologically relevant concentrations. The inhibitory concentration-50 (IC 50 ) were determined as 0.3 and 1.2 micromolar (µM) in BON-1 and QGP-1 cells respectively. Importantly, RPT-E-037 demonstrated selectivity, showing no adverse effects on normal islet cells (ABC-TC4286, AcceGen) at concentrations effective against tumor cells (reflected by its 40-folds higher IC 50 ). In addition, growth inhibitory effect of RPT-E-037 significantly rescued by nicotinic acid (niacin) treatment in BON-1 cells. Niacin also diminishes its colony reduction and apoptotic ability of RPT-E-037 in this cell line. The novel NAMPT inhibitor RPT-E-037 was shown to induce “DNA synthesis (S) phase” cell cycle arrest. However, niacin treatment switches “S phase” cell cycle arrest to “G0/G1 phase” cell cycle arrest. RPT-E-037 synergized with pNETs standard of care mTOR targeted agent everolimus in both BON-1 and QGP-1 cell lines leading to superior cell deaths (CI in vivo efficacy of RPT-E-037 in BON-1 and QGP-1 cell line derived xenografts (CDxs) are under way. Conclusion: For the first time, this study reveals the therapeutic potential of RPT-E-037, a new NAMPT inhibitor, for pNETs in preclinical models. RPT-E-037 shows promise as a novel NAMPT inhibitor and deserves further clinical investigation for pNETs.Generative AI was used for improving the language of the abstract.
Disclosure
M. Uddin, None.. A. Aboukameel, None.. S. F. Bannoura, None.. I. Muqbil, None.. H. Jimenez, None.. F. Khan, None.. R. Beydoun, None.. G. Dyson, None.. Y. Shi, None. M. N. Al Hallack, Ipsen Speaker. AstraZeneca Speaker. Guardant Health Speaker. Pfizer Speaker. Takeda Speaker. N. Vaishampayan, None. I. Azar, MJH Life Sciences Other, Honoraria. AstraZeneca Other, Consulting or Advisory Role. Genmab Nishant Gandhi Other, Consulting or Advisory Role. Caris Life Sciences Employment. S. Kim, None.. E. W. Bael, None.. M. Tobon, None.. K. Choucair, None.. W. Sukkari, None.. H. Imtiaz, None.. H. Chen, None. M. W. Saif, US World Meds [Oncologic Drug Advisory Committee] Other, Advisory Board. Uptodate Other, Honorarium. Amal Therapeutics ). Genentech, Inc. Other, Honorarium. IDEAYA Other, Honorarium. SpringWorks Therapeutics Other, Honorarium. Yivia Other, Honorarium. HCW Biologics Other, Honorarium. FLASCO Other, Speaker. R. M. Mohammad, None. P. Philip, Bayer Other, Honoraria. Ipsen Other, Honoraria. Incyte Other, Honoraria. Seagen Other, Honoraria. Taiho Pharmaceutical Other, Honoraria. Astellas Pharma Other, Honoraria. BioNTech SE Other, Honoraria. Novocure Other, Honoraria. TriSalus Life Sciences Other, Honoraria. SERVIER Other, Honoraria. Celgene Other, Consulting or Advisory. Ipsen Other, Consulting or Advisory. Merck Other, Consulting or Advisory. TriSalus Life Sciences Other, Consulting or Advisory. Daiichi Sankyo Other, Consulting or Advisory. SynCoreBio Other, Consulting or Advisory. Taiho Pharmaceutical Other, Consulting or Advisory. Incyte Other, Speaker. Bayer (Inst) ). Incyte (Inst) ). B. F. El Rayes, Seattle Genetics ). Exelixis Other, Advisory Board. Beigene Other, Advisory Board. AstraZeneca Other, Advisory Board. Merck ). Bristol-Myers Squibb ). Astra Zeneca ). Boehringer Ingelheim ). M. Wu, Remedy Plan, Inc. Stock Option. M. Schelle, Remedy Plan, Inc. Stock Option. Acrigen Biosciences Stock Option. B. Pasche, Merck & Co Inc ). Roche ). Novartis ). AstraZeneca ). Bristol Myers Squibb Co ). TheraBionic Inc Stock. TheraBionic GmbH Stock. A. S. Azmi, Guidepoint Other, consulting or advisory. Gerson Lehrman Group Other, consulting or advisory. Purple Biotech ). FanWave ). Colorado chromatography ). Blackstone Therapeutics ).
Cited in
Control: 2502 · Presentation Id: 8807 · Meeting 21436